Gestational exercise and intergenerational inheritance. Metabolic and functional outcomes in rat liver and skeletal muscle

Abstract

Maternal environmental exposure during gestational period may affect offspring risk for chronic diseases. Accordingly, maternal metabolic disturbances induced by high-fat high-sucrose (HFHS) diets can have a negative impact on offspring liver and skeletal muscle (SM) tissue phenotypes. In contrast, gestational exercise (GE) seems to favorably modulate deleterious stimuli induced by HFHS- diet consumption, not only in mothers but also in their offspring. However, the mechanisms associated to intergenerational inheritance of favorable metabolic outcomes in the offspring are far to be understood, as well as the role of epigenetic regulation in the offspring program. In order to contribute to increase the scientific knowledge in this field, the present PhD thesis comprises two literature review publications and three animal-based experimental papers that were developed using a gestational diabetes mellitus (GDM) model. Therefore, the goal was to analyze the potential role of an exercised model that combines voluntary free-running wheel (FRW) with forced endurance exercise, against liver and SM offspring metabolic and functional impairments. Our data revealed that GE counteracted the negative impact of HFHS maternal diet and sedentarism in offspring liver and SM morphology. Moreover, offspring from HFHS exercised mothers exhibited an improvement in liver and SM parameters of mitochondrial biogenesis, oxidative phosphorylation subunits protein content and respiratory capacity, associated to improvements in maximal exercise performance. Additionally, improvements in biomarkers of mitochondrial performance seems to be regulated, at least in part, by the role of miRNAs through epigenetic modifications inhered by the offspring generation. Ultimately, these findings shed light on the importance of maternal lifestyle, specifically the relevance of GE, on the phenotypic programming of the offspring against GDM-associated metabolic impairments and ultimately to an enhanced functional performance. Hopefully, evidence from the present PhD thesis can contribute to encourage mothers to engage in an active lifestyle before and during pregnancy aiming positive outcomes in their offspring.